Monthly mini-dose rituximab for primary anti-PLA2R-positive membranous nephropathy: a personalized approach

Abstract

Background: The currently recommended dose of rituximab for primary membranous nephropathy is as high as that for lymphoma. However, the clinical manifestations of membranous nephropathy vary widely. Therefore, achieving individualized treatment is a topic that needs to be explored. This study assessed the efficacy of monthly mini-dose rituximab monotherapy in patients with primary membranous nephropathy.

Methods: This retrospective study included 32 patients with primary membranous nephropathy treated at Peking University Third Hospital between March 2019 and January 2023. All patients were anti-phospholipase A2 receptor (PLA2R) antibody-positive and received rituximab 100 mg intravenously monthly for at least 3 months without other immunosuppressive therapy. Rituximab infusions were sustained until either remission of the nephrotic syndrome or a minimum serum anti-PLA2R titer ˂ 2 RU/mL was achieved.

Results: The baseline parameters included: proteinuria, 8.5 ± 3.6 g/day; serum albumin, 24.8 ± 3.4 g/L; and anti-PLA2R antibody, 160 (20-2659) RU/mL. B-cell depletion was achieved in 87.5% patients after the first dose of rituximab 100 mg and in 100% after the second equivalent dose. The median follow-up was 24 months (range 18-38). Twenty-seven (84%) patients achieved remission, with 11 (34%) patients achieving complete remission by last follow-up. The relapse-free survival from the last infusion was 13.5 months (range 3-27). Patients were stratified into the low-titer (< 150 RU/mL, n = 17) and high-titer groups (≥ 150 RU/mL, n = 15) based on the anti-PLA2R titer. Sex, age, urinary proteins, serum albumin, and estimated glomerular filtration rate at baseline did not differ significantly between the two groups. At 18 months, compared to the low-titer group, the rituximab dose (960 ± 387 vs 694 ± 270 mg, p = 0.030) was higher, while serum albumin (37.0 ± 5.4 vs 41.3 ± 5.4 g/L, p = 0.033) and the complete remission rate (13% vs 53%, p = 0.000) were both lower in the high-titer group.

Conclusions: Monthly rituximab 100 mg appeared as a potential effective regimen for treating anti-PLA2R-associated primary membranous nephropathy with a low anti-PLA2R titer. The lower the anti-PLA2R titer, the lower the rituximab dose required to achieve remission.

Trial registration: A retrospective study, registered at ChiCTR (ChiCTR2200057381) on March 10, 2022.

Keywords: Anti-phospholipase A2 receptor antibody; Membranous nephropathy; Mini-dose; Nephrotic syndrome; Rituximab.

Fig. 1

Flowchart of enrollment

Fig. 2

Immunological changes in individual patients before and after monthly mini-dose rituximab treatment. A. CD19 + B lymphocyte count; B. CD20 + B lymphocyte count; C. Anti-phospholipase A2 receptor antibody titer; D. Circulating peak and trough rituximab concentration(Peak: samples were obtained the next morning after rituximab infusion; trough: samples were acquired a couple of days before the next rituximab treatment)

Fig. 3

Comparison of the clinical data between different anti-PLA2R titer groups before and after monthly mini-dose rituximab treatment. A. Decrease in urinary protein excretion; B. Increase in serum albumin; C. Changes in the estimated glomerular filtration rate; D. Overall remission rate. Blue line: low anti-PLA2R titer group, red line: high anti-PLA2R titer group. PLA2R: phospholipase A2 receptor. *p < 0.05, ** p < 0.01